FDA Regulation

Recently, Reuters reported that “Drug companies generally don’t disclose all the reasons new medicines fail to win U.S. marketing approval, even though regulators often reject treatments over concerns about safety or effectiveness”.

Reporter Lisa Rapaport quotes Dr. Peter Lurie, FDA associate commissioner for public health strategy and analysis, saying “‘Only a minority of the press releases clearly stated that receipt of a complete response letter meant that marketing could not commence, and most findings associating the drug with a higher mortality rate went unmentioned.’” (emphasis added)

In her report, Rapaport notes that Dr. Lurie reviewed announcements by pharmaceutical companies following FDA disapproval released between 2008 and 2013 and found that “About half of the time, the complete response letters cited shortcomings in both safety and effectiveness. Out of 191 concerns about effectiveness raised in the letters, drugmakers disclosed a total of 30 in press releases, while companies shared 22 of 150 safety concerns.

Roughly half of the letters asked for new clinical trials to study safety or effectiveness; and in 59 percent of these cases companies disclosed this in a press release.”

This practice makes intuitive sense for drug companies, however cynical it is to admit. Why would pharma companies want to disclose precisely how a proposed product failed to meet FDA safety and efficacy requirements?

This actually raises an important issue for the FDA: should all proposed pharmaceutical products, not only approved drugs and devices, be a part of public knowledge? Companies whose stock is traded on the open market are already required to detail drug rejections (as is noted in the aforementioned Reuters piece), but not all drug companies are publicly held. Privately-held pharmaceutical corporations will argue that disapproved compounds consist in proprietary knowledge, and they may be right, public health concerns aside.

It nonetheless still is important to consider drugs that “may have been,” (or rather, drugs that failed to surmount the ever-weakening FDA approval process). Many drugs sold in America are disapproved upon initial FDA review, and following simple adjustments to study design, methodology, or statistical rigour are approved without meaningful changes to drug design. That is, the method used to test a drug’s effectiveness or safety can be adjusted, and a disapproved drug is made legal, without change to a drug’s chemical design.

With attention paid to disapproved drugs through open communication between pharmaceutical companies, the FDA, and the American public, consumers can understand more completely whether substantive changes were made to a drug’s design between initial disapproval and subsequent approval.

By no means would I suggest it is necessary, or would even be helpful, that the American populous attempt a measure of biochemical or pharmacological scrutiny when reviewing the FDA’s news ticker. That is the task of science journalists and healthcare analysts. As long is information regarding drug disapproval is available in full, dissemination to the public is possible, and that is a good thing.

Recently, a craniofacial distraction implant by DePuy Orthopaedics was recalled. This device, called the Craniomaxillofacial (CMF) Distraction System, “is a modular family of internal distraction devices that are used to gradually lengthen the mandible body and ramus” and indicated as “a bone stabilizer and lengthening (and/or transport) device for correction of congenital deficiencies or posttraumatic defects of the mandibular body and ramus, where gradual bone distraction is required,” for children less than one year old.

However, the FDA writes that “Infants are at the highest risk for injury if the device fails because sudden obstruction of the trachea can occur. This could lead to respiratory arrest, and result in death.” (emphasis added)

Again according to the FDA, “DePuy Synthes is recalling certain lots because the device may reverse direction and lose the desired distraction distance after surgery”, noting that “children or adults with the ability to maintain an open airway are at less risk for serious injury because failure of the device would not result in tracheal obstruction and could be medically reversible.”

Importantly, it is made clear that “In all patient populations, failure of the device may result in the need for surgical intervention to replace the failed device.”

To-date, fifteen people have been injured due to failure of the CMF Distraction System.

If you or a loved one used a CMF Distraction System and suffered injury as a result, you may be entitled to significant financial compensation through a CMF Distraction lawsuit. For a free, no-obligation case consultation, contact our team of CMF Distraction lawyers at the information provided below. We have the experience, resources, and skills required to win the justice you deserve. Call today and see how we can help.

The defendant companies are USPLabs, LLC (“USPLabs”) and General Nutrition Center Holdings Inc. (“GNC”). USPLabs sells a variety of energy and weight loss dietary supplements under the brand name of OxyElite Pro through GNC.

The complaint was filed in the U.S. District Court for the District of New Jersey. In it, Plaintiff Barot says he bought and used OxyElite Pro supplements while living in New Jersey between March 2010 and October 2011. He says he bought the product at a GNC store. Barot says OxyElite Pro was sold in New Jersey between January 2008 and November 2013.

In April 2012, the Food and Drug Administration warned USPLabs about the use of a dangerous stimulant called dimethylamylamine (“DMMA”) in its products. A class-action complaint followed and was resolved by a settlement agreement. Hogan v. USPLabs LLC, No. BC486925 (Cal. Super. Ct., L.A. County).

However, during and subsequent to Hogan v. USPLabs, LLC, Defendant USPLabs contained and or included another dangerous ingredient in OxyElite Pro called, Aegeline. Public health officials are currently investigating severe illnesses allegedly connected to Aegeline, including liver disease and hepatitis.

Plaintiff Barot points to medical records submitted to the FDA by the Hawaii Department of Health in which patients who used OxyElite Pro became severely ill. The complaint states that the use of the product was the only common factor among the patients and many became well again after stopping its use. Therefore, the complaint argues, the likelihood that OxyElite Pro caused the illnesses is strong.

While some consumers were lucky enough to get well after they ceased ingesting the dietary supplement, for others, the damage had already been done. Several patients sustained liver injuries that required transplantation. Tragically, one patient died before a transplant could be performed. As of February, OxyElite Pro has been linked to 97 cases of hepatitis.

On Oct. 11, 2013, the FDA issued a warning to USPLabs to stop distribution of all products containing aegeline. The company conducted a voluntary recall about one month later, but Barot says it failed to provide any notice to consumers.

Specifically, Barot says he and other potential class members suffered economic damage in buying USPLabs’ products, which they would not have taken had they known of aegeline’s potential adverse effects. He also alleges that inadequate labeling on the product constituted an unfair trade practice because the ingredients were unfit for safe use and that the defendant companies were unjustly enriched at the expense of consumers’ health.

Currently, at least 97 people have suffered severe hepatitis in connection with OxyElite Pro, and one person has died. The first reports of liver damage linked to OxyElite Pro came to light in May 2013, but the FDA was not aware of this until September of that year. Several months later, the manufacturer of OxyElite, USPLabs, issued a voluntary recall.

Scientists now believe that the questionable OxyElite ingredient, aegeline, is responsible for these cases of hepatitis, and the FDA has ordered USPLabs to discontinue its use.

Dr. Pieter Cohen of Harvard University published an article in The New England Journal of Medicine on this topic topic and explains that the hepatitis cases linked to OxyElite Pro are merely emblematic of a larger problem: the safety and efficacy of dietary supplements are not regulated by the FDA before products hit the shelves.

Cohen writes “The FDA’s delayed response — with its life-threatening consequences — is attributable to our woefully inadequate system for monitoring supplement safety. Americans spend more than $32 billion a year on more than 85,000 different combinations of vitamins, minerals, botanicals, amino acids, probiotics, and other supplement ingredients. Unlike prescription medications, supplements do not require premarketing approval before they reach store shelves. Under the Dietary Supplement Health and Education Act of 1994, anything labeled as a dietary supplement is assumed to be safe until proven otherwise. The FDA is charged with the unenviable task of identifying and removing dangerous supplements only after they have caused harm.”

He explains that in 2013 alone, his colleagues and FDA researchers identified two novel analogues of methamphetamine present in products currently available to consumers. One analogue was present in a sports drink, and the other analogue was present in nine dietary supplements. By law, none of these products were to be reviewed ad hoc by the FDA, a loophole in effect making lab animals out of consumers.

Though a US Senate bill sponsored by Dick Durbin (D-IL) and Richard Blumenthal (D-CT) is currently under review by committee that would ensure proper labeling of “vitamins, minerals, botanicals, probiotics, and other supplement ingredients,” Dr. Cohen states that this “would not improve the FDA’s ability to detect and remove dangerous supplements from store shelves.”

What is required is a more broadened reform of the approval processes for dietary supplements and other such products. It seems clear and obvious that anything consumed in our country should undergo rigorous testing before it becomes available on the market, particularly if a product advertises health benefits. While this could lengthen the time it takes before products may be sold and increase costs, any financial burden or wait time would be well worth the benefit of a more protected America.

A recent article in the Los Angeles Times discusses industry pushback against proposed federal legislation that would allow the manufacturers of generic pharmaceutical drugs the ability to “inform people about all known health risks” associated with various drugs produced. The Generic Pharmaceutical Association was quoted saying that the new regulations “would create ‘dangerous confusion’ and have ‘harmful consequences for patients.’”

This sentiment comes as a result of a report by independent consulting firm Matrix Global Advisors stating “the rule change would needlessly complicate the market and add $4 billion a year to already bloated healthcare costs.”

Alex Brill, lead author of the aforementioned report, states that this increase in cost would come as “‘Higher insurance premiums, self-insurance costs and reserve spending on product liability will likely force generic drug manufacturers to raise prices’” in an interview with the LA Times. That same LA Times piece also notes that the Matrix report was “sponsored” by none other than the Generic Pharmaceutical Association.

Obviously, the generic pharmaceutical industry wants to keep its costs down, but it is sad that this end seems valued over consumer safety. As it currently stands, the manufacturers of brand name drugs are required by the FDA to inform the public of newly-discovered hazards related to their medications. This does not apply to generic drugs manufacturers.

LA Times states that in response to this most recent ruling, the FDA has chosen to “empower generic makers to update their warning labels any time new risks become known, rather than wait for federal authorities to require a change.”

The reason that generics manufacturers are opposed to this change is that when label changes weren’t under their purview, companies could sit on data showing a health risk associated with their products without the legal obligation to act. Now, these companies would be obligated to make timely, effective label changes, which could hurt sales of the drug in question — as it should.

To that end, Congress passed the Drug Quality and Security Act (DQSA) on 11/27/2013, a law with two aims: to ensure the quality of compounded drugs, and to ensure the security of compounded drugs. Toward the goal of ensuring drug quality, the law “Establishes annual registration requirement for any outsourcing facility” (for clarity, “outsourcing facility” means compounding pharmacy), “Requires a facility to report biannually to the Secretary of Health and Human Services (HHS) on what drugs are compounded in the facility and to submit adverse event reports”, and “Subjects such facilities to a risk-based inspection schedule.” (DQSA)

Toward the goal of ensuring drug security, the law “Establishes requirements to facilitate the tracing of prescription drug products through the pharmaceutical supply distribution chain” (DQSA). According to an article by FDA Commissioner Dr. Margaret Hamburg, this will be a stepwise process taking ten years to become fully effective. At that point, the law “will require manufacturers, repackagers, wholesale drug distributors, and dispensers (other than most licensed health care practitioners) to provide product and transaction information with each sale and notify the FDA and other stakeholders of illegitimate products, which will result in improved detection and removal of potentially dangerous drugs from the supply chain.”

Jill Wechsler, Washington editor of the Pharmaceutical Technology blog, PharmaTech Talk, writes that of yet (just three months after the passage of DQSA), only 14 compounding pharmacies have registered with the FDA – of over 3,000 currently operating in the United States. However, these figures ought not to be discouraging, she writes, as “this initial activity reflects FDA’s fast action in implementing the Drug Quality and Security Act”.

Further, there is a disincentive for compounding pharmacies to register with the FDA including significant fees and the obligation to submit to federal regulations and inspections, and Wechsler writes the FDA is currently implementing three strategies to encourage compounding pharmacy registration. First, the FDA is asking “hospitals to exert their purchasing power to compel compounders to embrace the new regulatory system” by sending letters to “hospitals urging them to pressure the compounding pharmacies they buy from to sign up as outsourcing facilities. Support for this approach was recently voiced by executives at the Premier hospital system, which purchases drugs for hundreds of hospitals.”

Next, Commissioner Hamburg has sent letters to state governors and “members of state boards of pharmacy and state health officials” touting the benefits of the Drug Quality and Security Act, seeking state assistance in “dealing with distant compounders that ship into a state.”

Though there are certain disincentives for compounding pharmacies to register with the FDA, it must be made clear the possibilities of their commercial benefit and legal protection await.

Lastly, the FDA is aiming to encourage compounding pharmacy registration by re-establishing Pharmacy Compounding Advisory Committee, which will make new regulations. The committee will likely be composed of “leading experts in the field” and “nonvoting representatives of pharmaceutical manufacturers and of pharmacy compounders.”

Wechsler concludes, “One important task for FDA is to develop lists of drugs that may not be compounded and lists of bulk drug substances that comply with established standards and thus may be used in compounding. FDA plans to issue new regulations to update these lists. The agency also will continue proactive and for-cause inspections of compounding pharmacies and will ‘take aggressive action’ when necessary to protect the public health.”

Though I find it incredible that compounding pharmacies had not as yet been subject to federal inspection and other such requirements, DQSA is absolutely a step in the right direction.

Yesterday (1/16/2014) Reuters reported that an FDA advisory panel rejected a call by Johnson and Johnson to approve their anticoagulant Xarelto (rivaroxaban) for acute coronary syndrome by a vote of 10-0 with one abstention.

While Xarelto “is already used to treat and prevent deep vein thrombosis and pulmonary embolisms and to reduce the risk of stroke and blood clots in patients with an irregular heart beat that is not caused by heart problems”, due to a lack of data and a failure by the company to demonstrate the benefits of Xarelto outweigh the risk for bleeding associated with the drug, the FDA advisory panel decided that “Xarelto should not be approved to prevent further heart problems in patients who have recently suffered a heart attack”.

If the drug had been approved for acute coronary syndrome, it could be prescribed for “any condition brought on by a sudden, reduced blood flow to the heart, including heart attack and chest pain.”

Sadly, it seems Johnson and Johnson made its case based on evidence from only one research study. Dr. Stephen Grant, consulting professor of medicine at Stanford University School of Medicine, gave an interview to Reuters, stating “Looking at the overall study it wasn’t robust enough in terms of statistical significance to be considered a positive study, and with that it was not possible to look at subgroups.”

“Dr. Stephen Grant, deputy director of the FDA’s division of cardiovascular and renal drugs, said the benefit of the drug met the criteria required to approve a drug based on a single trial – namely, proof it was superior in some way to existing products.”

A recent article by Bill Berkrot and Ransdell Pierson (published in Reuters) reports on restrictions being lifted from the use of the drug Avandia. Avandia is a diabetes drug made by the company GlaxoSmithKline that was thought to increase the risk for heart attacks for people using the drug. The U.S. Food and Drug Administration conducted an investigation into the safety of the drug and found there was not a significant increase in risk for heart attacks with Avandia, and their recommendation led health regulators to lift the restrictions of use for the drug.

Type I diabetes is an autoimmune disease that inhibits the body from properly controlling the amount of sugar in the blood. Type I diabetics do not produce insulin, which acts like a key that allows sugar to enter the cells. Cells gain energy from sugar, and will die without the proper supply. Type II diabetes can come as a result of a poor diet and lack of exercise that causes the pancreas to form defective insulin molecules that do not adequately perform their function. Both types of diabetes are serious medical conditions that can be fatal if not properly handled.

A 2007 report that claimed Avandia was dangerous prompted a halting of the distribution of the drug from Europe, and resulted in restrictions on the sale of the drug in the US. The chemical name of Avandia is rosiglitazone had been one of the best selling medications for Glaxo, earning the company billions of dollars before rumors of the drugs dangerous characteristics came about. Despite the fact that recent studies have shown there is no increased risk for heart attack while using Avandia, it is still assumed the drug will only be prescribed to patients who have tried other diabetes medications without success. Only a small fraction of Americans continue to take Avandia since the restrictions were put in place.

Salmonella is a food-borne bacteria, typically present in meat and poultry products. An estimated 1.3 million illnesses can be attributed to Salmonella every year. To address outbreaks of salmonella, the US Department of Agriculture’s (USDA) Food and Safety Inspection Service (FSIS) has released its Salmonella Action Plan that outlines the steps it will take to address Salmonella contamination of meat and poultry products. The plan has been released to make meat and poultry products safer for consumption.

As reported by Adam Tarr of FSIS, one of the top priorities of the action plan is to modernize the outdated poultry slaughter inspection system. Focusing on food safety should help prevent at least 5,000 illnesses. Additionally, the plan includes enhancing sampling and testing programs, which will include the latest scientific information available, ensuring that the best available methods will be used to monitor the food products. Furthermore, the plan includes “several actions FSIS will take to drive innovations that will lower Salmonella contamination rates, including establishing new performance standards; developing new strategies for inspection and throughout the full farm-to-table continuum; addressing all potential sources of Salmonella; and focusing the Agency’s education and outreach tools on Salmonella.”

These new efforts are meant to build upon the previous work done by the USDA to lower contamination rates. In 2011, the new performance standards for Salmonella were set to reduce illnesses by 20,000 per year. After implementing these new strategies, Salmonella rates in young chickens have dropped over 75% since 2006. Hopefully, this will let us all breathe a little easier this holiday season.

Ellen Beck recently wrote an article for the “Smart Blog on Food and Beverage” website titled “FBI Makes Threats to U.S. Food Supply a Bigger Priority”, that discusses the food industry’s vulnerability to intentional food contamination. In light of all the terrorist attacks taking place throughout the world, the FBI is becoming increasingly concerned that food might be used to carry out a large scale attack on the American people, for intentional contamination can lead to widespread food borne illnesses that have the potential of infecting millions of people.

The FBI has been tracking incidents of intentional food contaminations and taking a closer look for ways to reduce these incidents from people or organizations that infect food supplies. Motives for these intentional food contaminations may include terrorism or economic gains. In recent years, a defense mission has been created through the FBI with the ability to activate thousands of agents to defend the food supply. This mission uses the Joint Terrorism Task Forces and Hazardous Evidence Response Teams to cover all possibilities and situations that may arise from an intentional food contamination attack.

Beefing up on the ability of the FBI to investigate and predict possible threats related to intentional food contamination started after the 2001 9/11 terrorist attacks. In Ellen Beck’s article she quotes FBI agent Thomas Rosato who states “We get the fact that because of its systemic nature, our food supply would be a very effective dispersal device for weapons of mass destruction”. While the FBI has a lot of experience with the investigatory process, the Bureau needs help and input from the Food and Drug Administration and other agencies that have intimate knowledge of how the American food systems work to be effective in preventing these kinds of attacks.

About this Blog

This blog chronicles legal and scientific news relating to personal injuries caused by defective drugs and medical devices. It is published by injury lawyer Justinian C. Lane, an attorney who takes a personal interest in each of his clients’ cases.